Advances in understanding the pathogenesis of systemic anaplastic large cell lymphomas

Summary The currently used 2008 World Health Organization classification recognizes two types of systemic anaplastic large T cell lymphoma according to ALK protein expression in tumour cells. First, the ‘anaplastic large cell lymphoma, ALK positive’ ( ALK + ALCL ) that is characterized by the presence of ALK gene rearrangements and consequent ALK protein expression, and, second, the ‘anaplastic large cell lymphoma, ALK negative’ ( ALK − ALCL ) that is a provisional entity lacking ALK protein expression but cannot be distinguished morphologically from ALK + ALCL . In this review we summarize the current knowledge on the genetic lesions and biological features that underlie the pathogenesis of ALK + and the ALK − ALCL and that can lead to the use of targeted anti‐cancer agents.